The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine: a chiral Weinreb amide equivalent
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Updated: Jun 21, 2026

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Alexander N Chernega1, Stephen G Davies, Christopher J Goodwin
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Abstract:
The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in > 98% ee, on a multigram (> 25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (> or = 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (> 98% de) after chromatography. Reductive cleavage with LiAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (> or = 94% ee). The auxiliary can be recovered in > 98% ee and recycled.
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